Thickening of bladder wall

What Causes Bladder Wall Thickening?

The muscular wall of your bladder tends to grow thicker if it has to work harder to urinate. It can also thicken if it becomes irritated and inflamed. Scarring of the bladder wall may also cause it to thicken.

Common causes of bladder wall thickening include:

Inflammation due to urinary tract infection (UTI)

A UTI is often the result of bacteria entering the urethra and then the bladder. These infections are more common among females than males.

UTIs are often associated with sexual intercourse, but a woman who isn’t sexually active can also develop a bladder infection. This is simply because of the amount of bacteria in and around the vagina.

One of the major responses to a UTI is inflammation of the bladder wall, a condition known as cystitis. Prolonged inflammation can lead to thickening of the wall. Some other causes of cystitis include inflammation triggered by cancer treatments, like radiation and chemotherapy, or prolonged use of a catheter.

Noncancerous tissue growths

Abnormal tissue growth in the bladder wall causes tumors to grow and the wall to thicken. Noncancerous (benign) tumors include papillomas. For some cases, viruses may be the cause of these growths.

Other benign bladder tumors include leiomyomas, but these are rare. They result from an overgrowth of smooth muscle cells in the bladder wall.

Fibromas are another benign bladder tumor. Abnormal growth of fibrous connective tissue in the bladder wall causes these.

Cancer

Cancerous (malignant) tumors tend to form first in the innermost lining of the bladder wall. This lining is known as the transitional epithelium.

The abnormal growth of cells in the bladder wall may be related to smoking tobacco or exposure to chemicals. Chronic irritation of the bladder wall or previous radiation exposure can also be the culprit.

Hemorrhagic cystitis

Sometimes irritation and inflammation of the bladder wall causes bleeding from the bladder lining. This is considered hemorrhagic cystitis. Causes may include:

  • radiation therapy
  • chemotherapy
  • an infection
  • exposure to certain chemicals, such as insecticides or dyes

Amyloidosis

Amyloid is a type of abnormal protein that’s made in your bone marrow. Amyloidosis is the buildup of amyloid in an organ. The bladder is one of several organs that can be vulnerable to this disease, but it’s not common.

End stage renal disease can trigger the abnormal growth of amyloid when dialysis doesn’t filter out amyloid that may be present. Autoimmune inflammatory diseases, such as rheumatoid arthritis, can also trigger amyloidosis, as well as other conditions. There’s also an inherited version called familial amyloidosis.

Bladder outlet obstruction

Bladder outlet obstruction (BOO) is a blockage at the base of the bladder where it empties into the urethra. For men, an enlarged prostate or prostate cancer can result in BOO. Other causes of BOO for men and women include:

  • bladder stones
  • tumors
  • scar tissue in the urethra

Ultrasound Thickness of Bladder Wall in Continent and Incontinent Women and Its Correlation with Cystometry

Objective. To compare bladder wall thickness in two kinds of urinary incontinent women—stress urinary incontinence (SUI) and overactive bladder (OAB) with urodynamic detrusor overactivity (DO), and to compare them with continent patients by ultrasound, also, correlate with cystometric results in incontinent women. Methods. 91 women were divided into the following groups: continent , SUI , and DO groups after clinical evaluation and urodynamic test (only in incontinent women). Transvaginal ultrasound was performed to the bladder wall thickness (BWT) measurement. The mean of BWT was calculated and data were analyzed with ANOVA and Turkey’s multiple comparison tests. Pearson’s correlation coefficient () was used to compare two variables. Receiver operating characteristic (ROC) curve was performed to study BWT as a diagnostic parameter. Results. BWT in DO group was significantly higher than that in the other groups . A moderate positive correlation was found between BWT and maximum bladder pressure during involuntary bladder contraction. There was no difference in BWT between SUI and continent groups. DO group had lower first desire to void and cystometric capacity. Maximum bladder pressure at detrusor contraction had a moderate positive correlation with BWT. The ROC revealed an area under the curve of 0.962 (95% CI, 0.90–1.01). Conclusions. DO patients have increased bladder wall thickness, lower first desire to void, and lower cystometric capacity. There was a moderate correlation between BWT and maximum bladder pressure during involuntary bladder contraction.

1. Introduction

Urinary incontinence is a common health problem associated with poor perception of personal health, impairment of quality of life, social isolation, and symptoms of depression . The most common subtypes of urinary incontinence are stress urinary incontinence (SUI), with leakage of urine during effort or physical exertion, and urgency urinary incontinence with the complaint of involuntary loss of urine associated with urgency (OAB) . The diagnosis in primary care can be done just based on patient’s complaints, or exams may be requested to further investigate the symptoms.

Urodynamic test tries to reproduce the situation in which patients’ complaints occur and therefore is considered an extension of patient history and physical examination in a controlled setting; however, it is not a mandatory exam for incontinence diagnosis . Detrusor overactivity (DO) is an urodynamic observation defined by involuntary detrusor contractions during the filling phase, which may be spontaneous or may be provoked. It is detectable in about half of the patients with OAB submitted to urodynamic test .

Ultrasound is a diagnostic method that is very much a part of general practice in obstetrics and gynecology and its role in urogynecology has increasing importance . When compared to other imaging exams, it is less invasive, nonradioactive, inexpensive, and widely available. In addition, ultrasound is the gold standard for measuring bladder volume and postvoiding residue, and it allows dynamic assessment of pelvic structures .

Bladder wall thickness (BWT) has been studied in incontinent patients and those with OAB especially those with DO who show higher values . Farag and Heesakkers , in a literature review, compared the various pathways of ultrasound to measure the BWT and they concluded that the study of BWT by transvaginal transducer is more appropriate. Oelke et al. compared the measurement of BWT obtained by conventional ultrasound with the automatic measurement performed by the BVM 6500 device. Although both show good reproducibility, the conventional measurement showed the smallest variation and it was more reliable. Kuhn et al. , comparing different ways to perform ultrasound to measure the BWT, found that vaginal measurement was more reliable than abdominal or perineal assessment.

The objective of this study was to compare the BWT in two kinds of urinary incontinent women, SUI and OAB with DO, and compare them with continent patients by transvaginal ultrasound, also, correlate with cystometric results in incontinent women.

2. Material and Methods

In a tertiary referral ambulatory, we selected women who were continent or with SUI or OAB. The study was approved by the Research Ethics Committee of Federal University of São Paulo (UNIFESP), and the volunteer women who agreed to participate gave consent form.

We included continent women with gynecological diseases or conditions other than urinary incontinence like miomas or adnexial cists.

Patients with mixed urinary incontinence, lower urinary tract diseases, bladder outlet obstruction, previous surgery for urinary incontinence, and current or recurrent urinary tract infection were not included. All patients were examined and pelvic organ prolapse quantification (POP-Q) was determined. Urodynamic test was performed before inclusion in this study and it followed the International Continence Society (ICS) recommendations using Dynapack MPX 816 four-channel urodynamic system (Dynamed, Sao Paulo, Brazil). The clinical diagnosis had to match the urodynamic test result.

Women were asked to void. Then, in supine position, ultrasound exam was performed using a SA-9900 (Samsung, Seoul, Korea) ultrasound machine equipped with a multifrequential transvaginal transducer (4–9 MHz). Using the method described by Haylen et al. , the residual volume was calculated to ensure that it was <50 mL. The bladder was visualized in the sagittal plane and then the probe was laterally moved 1 cm to achieve a clear view of the bladder and directed cranially to image the bladder in the parasagittal plane. At maximal magnification, the measurements were made perpendicular to the luminal surface of the bladder in the thickest part of trigone, dome of the bladder, and anterior wall of the bladder (Figure 1). BWT was considered the mean value of these three measurements. All exams were performed by the same physician (ENO, urogynecologist) who was also blinded to the incontinence diagnosis.


(a)
(b)
(a)
(b) Figure 1 Two-dimensional transvaginal ultrasound. (a) Measurement of anterior wall thickness of bladder (1). (b) Measurement of thickness wall in trigone bladder (1); measurement of thickness wall in dome bladder.

The data were transferred to the spreadsheet program Excel 2007 (Microsoft Corp., Redmond, WA, USA) and the statistical analysis was performed with GraphPad Prism version 5.0 for Windows (GraphPad Software, San Diego, CA). Analysis of variance (ANOVA) or Student’s -test was used to compare continuous variables. Post hoc multiple comparisons were performed using the Tukey’s multiple comparison tests. Pearson’s chi-squared test () was used to compare categorical variables. Mann-Whitney test was applied to compare two independent random samples. Pearson’s correlation coefficient () was used to compare linear dependence between two variables. In all analyses, we used a significance level of .

3. Results

A total of 91 patients with age between 18 and 81 were included in this study. Of these, 31 were continent, 30 had SUI, and 30 had urgency urinary incontinence (OAB with DO).

Table 1 Clinical characteristics of the patients.

BWT was higher in detrusor overactivity group and significantly different compared to SUI and continent groups (). There was no difference between SUI and continent groups (Figure 2).


Figure 2 Boxplot of the bladder wall thickness (BWT) according to the groups. SUI: stress urinary incontinence; DO: detrusor overactivity.

In Table 2, urodynamic findings are listed. In SUI group, 3 patients had intrinsic sphincter deficiency. In DO group, first desire to void and maximum cystometric capacity were significantly lower compared to SUI results.

Table 2 Urodynamic findings in women with stress urinary incontinence (SUI) or overactive bladder (OAB) with detrusor overactivity (DO).

The linear dependence in SUI group between BWT and first desire to void (, ), volume at leakage (, ), and maximum cystometric capacity (, ) was not significant.

Concerning OAB group, there was a moderate positive correlation between BWT and maximum vesical pressure at involuntary detrusor contraction (, ) (Figure 3). There was no significant correlation between BWT and first desire to void (, ) and maximum cystometric capacity (, ).


Figure 3 Scatter plot of correlation between bladder wall thickness (BWT) and maximum vesical pressure at involuntary detrusor contraction (IDC).

4. Discussion

The diagnosis of the type of incontinence only with the clinical assessment of patients can mislead to the right treatment. It is not uncommon that patients with OAB have involuntary detrusor contractions triggered by stress maneuver such as coughing or sneezing. In these cases, particularly, Giarenis et al. observed worse efficacy with tolterodine than women with involuntary detrusor contractions during cystometric filling phase of urodynamic test. It takes a good amount of self-perception to tell if the urinary loss is caused by sudden increase in intraabdominal pressure or by a detrusor contraction. Also, different diseases share common lower urinary tract symptoms and many times a consistent diagnosis is not reached . Questionnaires of quality of life, bladder diaries, and visual analog scales are valuable to expand the understanding and bothersome of the symptoms but provide only subjective data.

Currently, when clinical assessment of urinary incontinence is compared to urodynamic test, there is lack of a gold standard . Clarke considered the urodynamic test inappropriate to diagnose and introduced treatment based only in symptoms, as he found DO in 64% of the patients with SUI. Urodynamic test can provide valuable information of the underlying pathophysiology, but its intra- and interobserver reproducibility is not good .

Healthy patients have BWT measurement ranging from 3 to 5 mm . Conditions such as infection, pelvic radiation, pelvic surgery, neurological disease, cancer, and bladder outlet obstruction can cause thickening of the bladder wall associated to other sonographic signals . The study of BWT has brought the question if it is possible to diagnose OAB by a “cut-off” value measured by ultrasound. Khullar and Cardozo proposed 5 mm as a cut-off value to discriminate detrusor overactivity, while Robinson et al. considered 6 mm to the diagnose of OAB in patients without evidence of SUI. Kuhn et al. with a cut-off value of 5.6 mm found sensitivity of 83.3% and specificity of 87.5% in distinguishing between OAB and bladder obstruction. Serati et al. compared BWT in different forms of incontinence and concluded that a “cut-off” value of 6.5 mm could distinguish patients with detrusor overactivity, pure or associated with SUI, but it could not replace urodynamic test.

An important question is if we are looking to the right point. The diagnosis of DO is controversy. DO is present in only 40–60% of the OAB patients . Although urodynamic test is the only method to its diagnosis, the interobserver variation in evaluation of the same exam is high . DO is not exclusive of OAB patients; asymptomatic patients may present DO during urodynamic test when the saline solution is instilled very fast or too cold.

It is unknown if involuntary detrusor contraction is the cause of urgency at storage phase or that other types of lower urinary tract dysfunction can cause OAB complaints . Normal bladder physiology includes phasic contractions of low magnitude with frequency of dozens per minute, thus promoting a better adjustment of the bladder surface to urine filling . The detrusor of OAB patients presents biochemical changes, which have different cellular ultrastructure and tissue macrostructure leading to more contractility and resulting in hypertrophy of the detrusor muscle .

Using ICS’s definition of OAB syndrome, based only on symptoms, can lead to a heterogeneous group, as women with different physiopathologies present with the core complaint of urinary urgency. In a different approach, we aimed to study a homogeneous group only including women who not only complained of urgency, but were also incontinent and with presence of DO at urodynamic test. Women with DO experience more significant impairment to their quality of life and have a greater degree of bladder dysfunction . Our finding of higher values of BWT associated with higher vesical pressure at involuntary detrusor contraction concurs with the background of OAB. Also, there was a moderate positive relation between intensity of OAB and BWT.

We decided not to include patients with mixed urinary incontinence because of the difficulty to determine the “amount” of troublesome of each component of this group.

The time lapse necessary to increase the BWT from normal values is a question that remains without response. To our knowledge, it is not demonstrated yet.

According to the definition of OAB suggested by the ICS, the need to detect DO loses importance. On the other hand, it seems that increased BWT, as a result of repeated DO, is linked to clinical symptoms, as Panayi et al. observed that women with BWT greater than 5 mm had a visual analog scale of urgency significantly higher when compared to controls. In a recent article, Abou-Gamrah et al. found 4.78 mm of BWT the best cut-off value for prediction of OAB in patients with lower urinary tract symptoms.

As a diagnostic tool of urinary incontinence, we agree that BWT cannot replace urodynamic test. Nonetheless, our findings encouraged us to consider it as an “index” of detrusor activity.

One of the strengths of this paper is the observation that the BWT of the SUI patients and that of normal women are similar and significantly thinner than that of the DO patients, the most severe form of OAB. For our knowledge this is the first study that observed the BWT in SUI. The urodynamic evaluation in incontinent women and correlation with ultrasound findings are also the strengths of this paper. On the other hand, the weakness of this paper was that we did not investigate BWT of mixed urinary incontinence patients.

In summary, we believe that the thickening of the bladder wall is itself an important hallmark in OAB patients mainly when the clinic is not compatible with urodynamic test or in women not responsive to anticholinergics.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Interstitial Cystitis: Signs, Symptoms, and Treatment

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Interstitial cystitis (IC) is a painful condition in which the bladder wall becomes irritated and inflamed.

Chronic irritation can cause scarring and thickening of the bladder wall, making the bladder very stiff and unable to hold a normal amount of urine.

Historically, IC was considered to be a women’s issue that affected a small number of individuals. But the RAND Interstitial Cystitis Epidemiology Study (RICE) — the largest to date on IC — revealed that the condition affects 3 to 8 million women. (1)

Interstitial cystitis does not discriminate based on age or gender. The Interstitial Cystitis Association estimates 4 to 12 million men and women in the United States have IC. Although the condition can start in childhood, there’s not a proper estimate of the prevalence in children. (2)

And while there’s still much more IC discovery to be done, medical professionals say recent research has offered clues about treatment.

“Some of the best research now shows that this isn’t necessarily primarily a bladder condition,” says Nicole Cozean, CSCS, founder of the PelvicSanity clinic in Laguna Hills, California and coauthor of The Interstitial Cystitis Solution. “It’s a chronic pain condition that sometimes affects the bladder, but 90 percent of people with interstitial cystitis also have some form of pelvic floor dysfunction.”

When the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) completed phase one of its multidisciplinary approach to the study of chronic pelvic pain (MAPP) in 2016, it found that IC is indeed also a pain condition. (3) Women with IC exhibited white matter brain abnormalities in several different brain regions. These changes are attributed to brain changes that occur in individuals suffering from painful conditions.

Phase two of the study was scheduled to end in December 2018, but Dr. Cozean estimates results won’t be published until late 2019, at the earliest. (4)

What Causes Interstitial Cystitis?

IC is a spectrum disorder that can be mild in some patients and horribly severe in others. It can also occur in flares, says urologist Christian O. Twiss, MD, director of female urology, pelvic medicine, and pelvic reconstructive surgery at Banner — University Medical Center Tucson in Arizona.

Doctors don’t know the exact cause of interstitial cystitis, but they do know that it’s not an infection.

Some research, including a study published in September 2017 in the journal BMC Chemistry, has indicated that people with interstitial cystitis may produce a protein called antiproliferative factor that makes the bladder sensitive to urine. (5)

But most researchers believe that there may be a combination of causes.

Some risk factors for interstitial cystitis include:

Damage to the Bladder Surgery or other types of trauma may damage the bladder, contributing to this condition.

Bladder Distention The inability to empty your bladder for long periods of time has been associated with interstitial cystitis.

Nerve Damage Spinal cord trauma and inflammation of the pelvic nerves have been suspected as causes.

Other Inflammatory Diseases Women with irritable bowel syndrome (IBS), fibromyalgia, allergies, and asthma may be at higher risk for interstitial cystitis.

Sexual Abuse Some studies have found a relationship between childhood sexual abuse and interstitial cystitis, but these findings are still being debated. (6)

RELATED: Excessive Sitting Can Harm Your Urinary Tract, a New Study Finds

IC Symptoms and the Irritants That Can Cause a Flare-Up

Symptoms of interstitial cystitis may go away for a while, only to return months or even years later.

Changes in the bladder due to interstitial cystitis can cause the following symptoms:

Pain Pressure felt around the bladder and pelvic area can produce discomfort or pain that ranges from mild to very severe.

Pain is usually relieved after urinating. Men may feel pain in the area of the penis and scrotum.

Frequent urination Because the bladder becomes stiff and loses elasticity, people with interstitial cystitis have to urinate frequently both day and night.

“Normal is between six and eight times a day,” Cozean says. In severe cases of interstitial cystitis, a person may need to urinate up to 60 times per day.

Urgency The need to urinate can be intense and hard to control.

Sexual Dysfunction Many people with interstitial cystitis experience pain during sexual intercourse.

Nocturia This is a condition in which you wake up during the night with the urge to pee.

How Diet Can Help Relieve IC Symptoms

Avoiding foods that cause bladder irritation can help to relieve some symptoms of interstitial cystitis.

Common irritant foods include:

  • Tomatoes
  • Spices
  • Chocolate
  • Caffeine
  • Alcohol
  • Carbonated drinks
  • Citrus products
  • Artificial sweeteners

It might help to keep a diary of what foods seem to make your symptoms worse. (6)

The Tiers of IC Treatment Options

“The problem with IC is not only is it a poorly understood disease, but it tends to be chronic,” says Dr. Twiss. “It’s often a disease that’s managed over time and not cured.”

The American Urological Association recommends starting with more conservative therapies, before gradually moving to more invasive treatments when “symptom control is inadequate for acceptable quality of life.” (7)

Since IC commonly coincides with pelvic floor dysfunction, Cozean recommends starting with a pelvic floor physical therapist. It’s the AUA’s first medical recommendation, according to guidelines published in December 2015 in the journal Translational Andrology and Urology, and the only treatment with an evidence grade of “A.” Whether you go down the road of more bladder-centered treatments or more pain-centered treatments, the pelvic physical therapist can help to home in on what each individual patient should do first, second, and third, she says.

Twiss also refers many patients to a pelvic floor physical therapist early on in treatment. In addition, he encourages patients to identify flare-up triggers, such as types of food and fluid volume intake.

Oral medication can also help you to get relief from IC. Elmiron (pentosan polysulfate) has been approved by the U.S. Food and Drug Administration (FDA) for treating the condition. It works by protecting the bladder wall from urine irritation. Elmiron does not work for everyone and it may take several months to take effect.

The antidepressant medication Elavil (amitriptyline) is sometimes used to relieve pain and reduce bladder spasms. (7)

Other drugs that may be used include pain relievers and antihistamines.

The next tiers of treatment include electrical stimulations call neuromodulation, various levels of pain management, and Botox injections into the bladder. (7)

Twiss says he often sees bladder instillations, where a small amount of liquid medicine is inserted into the bladder, essentially “washing” it, as well as bladder pacemakers. As a last resort, a patient may have their nonfunctional bladder removed.

“IC is a bladder condition, a pelvic floor muscle condition, and a lot of times a nervous system condition as well,” says Cozean. “All three of those aspects need to be treated in some form or fashion in order for healing to occur.”

Additional reporting by Kalah Siegel.

Two Cases of Metastatic Bladder Cancers Showing Diffuse Thickening of the Bladder Wall

Abstract

Metastatic bladder cancer showing diffuse thickening of the bladder wall is very rare. We report two cases of metastatic bladder cancer arising from a stomach cancer and acute lymphocytic leukemia. Hydronephrosis and diffuse thickening of the bladder wall were revealed by ultrasonography and computed tomography. Transurethral biopsy and percutaneous whole wall needle biopsy of the bladder were useful for diagnosis. The possibility of metastasis or recurrence of prior and other malignancies should therefore be considered when the clinical features described here are encountered.

Introduction

Metastatic bladder cancer is rare. Most cases can be visualized endoscopically. We demonstrate here an atypical type of metastasis to the urinary bladder with diffuse wall thickening rather than a papilloma phenotype. We also review the literature on metastatic bladder cancers with special reference to the phenotype that can be classified into two types, protuberant and diffuse type, on the basis of radiological findings.

Case Reports

Case 1

A 43-year-old male initially presented with acute lymphocytic leukemia. Systemic chemotherapy and bone marrow transplantation were performed in 1991. Two years later, pain on urination and gross hematuria appeared. Urine cytology disclosed no malignancy. Whereas an intravenous urogram showed bilateral hydronephrosis, cystoscopy revealed no tumor. However, computed tomography demon strated diffuse wall thickening of the bladder (Fig. lA) and transurethral and percutaneous whole waIl needle biopsies were performed. From the results of pathological examination a diagnosis of bladder metastasis of acute lymphocytic leukemia was concluded (Fig. 2). After systemic chemotherapy and radiation therapy, the wall thickening of the bladder was improved (Fig. 1B), but he died 2 years later because of relapse with multiple metastasis of skin, right retroperitoneal space, right testis, stomach and mediastinum.

Figure 1

(A) Computed tomography shows diffuse thickening of the urinary bladder wall. (B) The wall thickening of the bladder was improved after chemotherapy and radiation therapy.

Figure 1

(A) Computed tomography shows diffuse thickening of the urinary bladder wall. (B) The wall thickening of the bladder was improved after chemotherapy and radiation therapy.

Figure 2

(A) The specimen of whole wall biopsy in Case I (×4), Widepread leukemia cells were observed, (8) Leukemia cells (× 120).

Figure 2

(A) The specimen of whole wall biopsy in Case I (×4), Widepread leukemia cells were observed, (8) Leukemia cells (× 120).

Case 2

A 57-year-old female underwent surgery for a Borrman IV-type poorly differentiated adenocarcinoma of the stomach. Two years after gastrectomy, a sense of residual urine and incontinence appeared. Hematopyuria was not detected on urinalysis and urine cytology disclosed no malignancy. An intravenous urogram showed right hydronephrosis. Ultrasonography (Fig. 3A) and computed tomography (Fig. 3B) revealed diffuse thickening of the bladder wall and hydronephrosis.We performed transurethral and percutaneous whole wall needle biopsies. The pathological examination demonstrated bladder metastasis from the previous stomach cancer (Fig. 4). No other metastatic lesion was detected. After systemic chemotherapy with 5-FU and CDDP, the wall thickening of the bladder was slightly improved radiologically (Fig. 3C). After 12 months, she is still alive and well. The chemotherapy is performed reiteratively.

Discussion

Metastatic neoplasms in the bladder are unusual, accounting for less than 2% of all bladder tumors (1). The most common associated primaries are malignant melanoma and stomach and breast cancers (2).

Figure 3

(A) Ultrasonography shows diffuse thickening of the urinary bladder wall. (B) Computed tomography shows diffuse thickening of the urinary bladder wall. (e ) The wall thickening of the bladder was slightly improved after chemotherapy, A urethral stent was inserted into the left ureter.

Figure 3

(A) Ultrasonography shows diffuse thickening of the urinary bladder wall. (B) Computed tomography shows diffuse thickening of the urinary bladder wall. (e ) The wall thickening of the bladder was slightly improved after chemotherapy, A urethral stent was inserted into the left ureter.

The metastatic bladder cancer can be classified into two types radiologically and macroscopically: protuberant and diffuse type. Most are protuberant in which gross hematuria is generally observed, greatly facilitating diagnosis. In contrast, the diffuse type is very rare and only two cases have been reported (3,4). These cases were characterized by irritable bladder symptom s without gross hematuria and presented diagnostic difficulties. As demonstrated here, ultrasonography and computed tomography are useful for visualizing diffuse thickening of the bladder wall.

Figure 4

Adenocarcinoma resembling prior stomach cancer infiltrates into muscle layer of the bladder (×80).

Figure 4

Adenocarcinoma resembling prior stomach cancer infiltrates into muscle layer of the bladder (×80).

The mechanism of cancer spread to the bladder is controversial. Three theories have been proposed for metastatic renal cell carcinoma cases (5–9): direct extension, implantation and retrograde venous embolism of tumor cells from the renal vein into the numerous venous connections of the left renal vein. With stomach cancer and leukemia, intraperitoneal dissemination, hematogenous or lymphatic spread to the urinary tract must be considered. Our cases indicate that whole wall biopsies of the bladder greatly aid diagnosis, in addition to transurethral biopsy.

Chemotherapy for management of diffuse-type lesions was performed in all cases. The prognosis of metastatic bladder cancers is poor in general, and determination of the best approach for control of the diffuse type awaits more cases.

1 Roberts DI . Secondary neoplasms of the genito-urinary tract, Br J Urol, 1978, vol. 50 pg. 68 2 Ganem EJ , Batal JT . Secondary malignant tumors of the urinary bladder metastatic from primary foci in distant organs, J Urol, 1956, vol. 75 pg. 965 3 Miyazaki H , Yamanaka N . A case of metastatic urinary bladder tumor from gastric remnant carcinoma, Hinyokika Kiyo, 1986, vol. 32 (pg. 1145-8) (in Japanese) 4 Nakamura K , Hihara T , Nishiumi T , Yoneyama K . A case of metastatic urinary bladder tumor from gastric remnant carcinoma, Hinyokika Kiyo, 1992, vol. 38 (pg. 845-7) (in Japanese) 5 Abeshouse BS . Metastasis to ureters and urinary bladder from renal carcinoma; report of 2 cases, J Int Coli Surg, 1956, vol. 25 pg. 117 6 Heslin JE , Milner WA , Garlick WB . Lower urinary tract implants or metastases from clear cell carcinoma, J Urol, 1955, vol. 73 pg. 39 7 Shaw RE . Metastasis to the bladder from carcinoma of the kidney, BrJ Surg, 1961, vol. 48 pg. 420 8 Bolkier M , Moskovitz B , Munichor M , Genesin Y , Levin DR . Metastatic renal cell carcinoma to the bladder, Urol Int, 1993, vol. 50 (pg. 101-3) 9 Chinegwundoh FI , Khor T , Leedham PW . Bladder metastasis from renal cell carcinoma, Br J Urol, 1997, vol. 97 (pg. 650-1) © 1999 Foundation for Promotion of Cancer Research

Macroscopic Hematuria and a Bladder Mass: Eosinophilic Cystitis in a 7-Year-Old Boy

We report a case of eosinophilic cystitis in a 7-year-old boy with a history of atopic symptoms, with focus on the radiological findings. He presented with hematuria and dysuria and ultrasonography (US) showed irregular bladder wall thickening resembling a bladder mass. CT urography did not characterize the lesion any further and showed no local or distant spread. Biopsies revealed eosinophilic cystitis, a benign inflammatory condition. We found that US characterized the lesion at least as well as CT and should be the first choice of imaging. When staging is considered before biopsy, MRI should be preferred to CT. There are no specific radiological signs of eosinophilic cystitis. On follow-up, US was a safe, cost-effective imaging modality, but findings should be interpreted in a clinical context. In a child with hematuria and a bladder mass, eosinophilic cystitis is a relevant but rare differential diagnosis, especially when there is a known atopic history.

The aim of this paper is to draw attention to the presenting symptoms and the radiologic evaluation of eosinophilic cystitis in childhood. Eosinophilic cystitis is an inflammatory condition characterized by eosinophilic infiltration of the bladder wall. It is rare amongst children with only 59 cases in the literature to date . In a review of 54 cases, the mean age of presentation was 6.7 years, with an overweight of male cases . The etiology is unknown . A tumor-like presentation on imaging has been reported previously, and the condition therefore requires thorough diagnostics to rule out malignant disease. We present a typical case of this atypical disease with focus on the radiological aspects of diagnosis and follow-up.

2. Case Presentation

A 7-year-old boy was referred to a secondary pediatric centre with gross hematuria and dysuria.

His previous medical history included atopic symptoms (wheeze, rhinitis, throat clearing, and cough), but, despite diagnostic evaluation, no asthma or allergies had been diagnosed. Physical examination revealed mild tenderness to palpation over the bladder. Urinalysis was positive for blood and protein. Blood creatinine was elevated to 56 μmol/L (26–49 μmol/L); infection parameters were normal. It was suspected that he suffered from urinary tract infection and antibiotic treatment was initiated, but the urine culture turned out to be negative. He had elevated IgE 665 ie (<400 ie) and slight eosinophilia in the blood 0.84 109/L (<50 109/L). All other hematologic parameters were normal: hemoglobin 7.8 mmol/L (6.5–8.9 mmol/L), white blood cell count 8.5 109/L (4.5–12.5 109/L), neutrophils 4.43 109/L (1.8–8.9 109/L), lymphocytes 2.5 109/L (1.0–4.7 109/L), and platelets 337 109/L (165–435 109/L).

One week later, he was readmitted due to recurrent terminal hematuria. Ultrasonography (US) showed right-sided hydronephrosis and hydroureter with distal occlusion by thickened ureter wall. Extending from the right ureter ostium, there was very irregular thickening of the posterior bladder wall, up to 1 cm, and Doppler flow within the wall (Figure 1). US diagnosis was infection sequelae or tumor. An acute CT urography was made to further characterize the changes in the right kidney and ureter. It confirmed the findings of the ultrasound (Figure 2) and showed contrast retention in the right kidney and pelvis but did not characterize the lesions further.

Figure 1 Ultrasound showed irregular bladder wall thickening of up to 1 cm resembling a tumor and Doppler flow within the wall.
Figure 2 CT confirmed the finding of irregular bladder wall thickening but did not characterize the bladder lesion as well as US. Coronal reconstruction with 8 mm slice thickness and digital optimization.

He was then transferred to a tertiary centre. A cystoscopy showed edematous mucosa with bullous excrescences from the trigonum to the right ostium and findings were very suspicious of neoplasia. A JJ catheter was inserted.

The biopsies showed eosinophilic cystitis and no sign of malignancy (Figure 3).

Figure 3 A biopsy from the bladder mucosa showing pronounced eosinophilia with free stomal granules (200).

The patient was treated empirically with antihistamine (Desloratadine 5 mg bd) and NSAID (Naproxen 5 mg/kg bd) and recovered clinically and paraclinically within 6–8 weeks. Before that he was treated with anticholinergica (Oxybutynin 2.5 mg bd) without effect. MRI after one month showed thickening of the right ureter wall and discrete bladder wall thickening. T2-weighted sequences showed homogeneous low signal intensity of the bladder wall (Figure 4).

Figure 4 Axial T2-weighted MRI after one month showed discrete bladder wall thickening with homogenous low signal intensity (arrow).

US and cystoscopy after 3 months showed marked regression and biopsies showed nonspecific reactive changes. At removal of the JJ catheter after 7 months, the bladder looked near normal at cystoscopy. US showed slight irregular bladder wall thickening. One year later, US showed low bladder volume; thus, wall thickness could not be evaluated.

The patient was rereferred at the age of 9 years with gross hematuria and dysuria, frequent throat clearing, epigastric stomach pain, and acid reflux. The eosinophilic blood cell count was normal and US showed slight thickening of the bladder wall of up to 5 mm (Figure 5). Treatment with antihistamine for 6 weeks eliminated all symptoms. After 8 weeks, US showed persisting slight bladder wall thickening of up to 3 mm.

Figure 5 Ultrasound at clinical recurrence showed thickening of the bladder wall of up to 5 mm.

3. Discussion

Our patient presented with macroscopic hematuria and symptoms typical of cystitis. Urinalysis was not consistent with urinary tract infection, though. This fact should lead to the consideration of other diagnoses. Eosinophilic cystitis, though rare, is a relevant differential diagnosis, especially in a patient with a known atopic history. Macroscopic hematuria in a child can be a symptom of severe renal or urinary tract disease, and immediate evaluation is recommended by the Danish Pediatric Society . The evaluation includes US of the kidneys and urinary tract, which in our case showed bladder wall thickening resembling a bladder mass.

A pseudotumoral appearance of (hemorrhagic) cystitis has been described in viral cystitis, being caused by chemotherapy or indwelling catheters, granulomatous cystitis, inflammatory myofibroblastic tumor, and eosinophilic cystitis .

Benign bladder lesions in children include several rare entities such as fibromas, hemangiomas, schwannomas, hematomas, leiomyomas, endometriomas, and transitional cell papillomas.

Malignant lesions include rhabdomyosarcomas (RMS), leiomyosarcomas, urothelial carcinomas, and secondary involvement such as lymphomas, with RMS being by far the most common .

Sonographically, eosinophilic cystitis can present as concentric bladder wall thickening or a more focal, tumor-like appearance as in our case. Hydroureteronephrosis was seen in other cases too .

To our knowledge, no specific US signs of eosinophilic cystitis have been reported.

Rosenberg et al. reported 17 children with benign cystitis in whom imaging mimicked RMS. They concluded that sonographic findings of isoechoic bladder wall thickening (focal, multifocal, or circumferential distribution), intact mucosa, and bullous lesions strongly suggested inflammation and not malignancy. Also, changing mass contour and thickness with increasing bladder filling should be signs of inflammatory thickening .

RMS has a highly variable appearance on US, but polypoid projection into the bladder lumen makes this diagnosis more likely .

Color Doppler US can be useful, as some differential diagnoses such as hematomas can be excluded if Doppler flow is missing.

In our case, CT did not characterize the bladder lesion any further. As RMS is a potential and common differential diagnosis, however, a CT scan can be useful to assess any local or distant spread (staging). This is also well examined with MRI though , and when the setting and logistics allow for it, we recommend that MRI should be preferred in the pediatric population to avoid potentially harmful radiation exposure (following the ALARA principle). In our case, cystoscopy and biopsy could well have been the next step after initial ultrasound, but if a lesion turns out to be malignant, biopsy potentially could have led to seeding of tumor cells. The relevance of the follow-up cystoscopy performed can be discussed.

Tamai et al. report a case of eosinophilic cystitis in an 8-year-old girl where MRI showed distinct low signal intensity on T2-weighted images, which was suggested to represent high cellularity due to massive eosinophilic infiltration . Eosinophilic cystitis has been reported isointense on T2-weighted sequences in the adult population . In our case, MRI was used in early follow-up and gave a clear impression of the remaining extent of the disease.

The normal bladder wall thickness in children depends on bladder volume. A normal bladder wall thickness of up to 1.5–3 mm (full bladder) has been found . Our patient had continuing bladder wall thickening on follow-up US. This could be due to chronic postinflammatory changes after the initial episode, consistent with biopsy findings of nonspecific reactive changes after 3 months. The significance of bladder wall thickening found by US at the time of clinical recurrence thus remains unclear and treatment relied on clinical presentation. Indeed, slight bladder wall thickening persisted despite clear effect on symptoms.

4. Conclusion

In a child with hematuria and clinical cystitis, but sterile urine, eosinophilic cystitis is a relevant but rare differential diagnosis, especially when there is a known atopic history. US should be the first choice of imaging and MRI should be preferred to CT when staging is considered before biopsy. Eosinophilic cystitis can present as a bladder tumor radiologically and macroscopically and since there are no specific radiological signs, biopsy remains required. US is a safe, cost-effective imaging modality on follow-up, but findings should be interpreted in a clinical context.

Competing Interests

The authors declare that there are no financial or other competing interests regarding the publication of this paper.

ORIGINAL ARTICLE

Year : 2018 | Volume : 29 | Issue : 3 | Page : 151-155

Urinary bladder thickness, tumor antigen, and lower urinary tract symptoms in a low Schistosoma haematobium-endemic rural community of Nigeria
Oyetunde Oyeyemi1, Adekunle Adefalujo2, Kolawole Ayeni3, Williams Nabofa4, Chinomso Nwozichi5, Adeyemi Dada6, Adebola Yusuf2
1 Department of Basic Sciences, Babcock University, Ilishan Remo, Ogun State; Department of Biological Sciences, University of Medical Sciences, Ondo, Ondo State, Nigeria
2 Department of Radio-Diagnosis, Babcock University Teaching Hospital, Ilishan Remo, Ogun State, Nigeria
3 Department of Microbiology, Babcock University, Ilishan Remo, Ogun State, Nigeria
4 Department of Physiology, Babcock University, Ilishan Remo, Ogun State, Nigeria
5 Department of Adult Health Nursing, School of Nursing, Babcock University, Ilishan Remo, Ogun State, Nigeria
6 Department of Chemical Pathology, Babcock University Teaching Hospital, Ilishan Remo, Ogun State, Nigeria

Date of Web Publication 27-Jun-2018

Correspondence Address:
Oyetunde Oyeyemi
Department of Biological Sciences, University of Medical Sciences, Ondo, Ondo State
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/UROS.UROS_3_17

Abstract

Objective: Bladder tumor antigen (BTA) is a common biomarker for urothelial carcinoma while bladder wall thickening (BWT) is a sign of urinary bladder irritation which suggests cystitis or early-stage bladder cancer pathology, most especially in the absence of bladder outlet obstruction. The aim of this study was to find the incidence of urinary bladder thickness and evaluate the relationship between BTA and BWT in a low schistosomiasis-endemic Nigerian village. Materials and Methods: The study was descriptive and cross-sectional. Freshly passed mid-day urine samples of 56 individuals were screened using chemical reagent strips and then diagnosed microscopically for Schistosoma haematobium. Subsequent follow-up involving ultrasound examination was carried out on distended bladder. The lower urinary tract symptoms (LUTS) were also recorded. Urinary BTA analysis was carried out on the urine samples using enzyme-linked immunosorbent assay. Results: The prevalence of urogenital schistosomiasis in the area was 3.6%. The overall prevalence of human BTA and BWT in the individuals was 44.6 and 35.7%, respectively. The LUTS were associated with BWT (P = 0.004; odds ratio = 6.0; 95% confidence interval = 1.8–20.3). BTA, BWT, and LUTS were not sex and age dependent (P > 0.05). In addition, there was no association between urinary BTA, BWT, and LUTS (P > 0.05). The sensitivity of BWT and LUTS (60.0%) was improved than when either was used to diagnose BTA. Conclusion: The high occurrence of BTA and BWT in the individuals suggests that they may be prone to urothelial carcinoma and urinary bladder irritation, respectively. The role of urogenital schistosomiasis in urinary BTA levels needs to be further explored.

Keywords: Bladder tumor antigen, bladder wall thickness, lower urinary tract symptoms, urogenital schistosomiasis, Nigeria

How to cite this article:
Oyeyemi O, Adefalujo A, Ayeni K, Nabofa W, Nwozichi C, Dada A, Yusuf A. Urinary bladder thickness, tumor antigen, and lower urinary tract symptoms in a low Schistosoma haematobium-endemic rural community of Nigeria. Urol Sci 2018;29:151-5

Introduction

The last decade epidemiological statistics on bladder cancer ranked it as the 11th most commonly diagnosed cancer and the 14th leading cause of cancer-associated deaths worldwide, with 382,700 estimated new cases and 150,300 deaths in 2008. Cystoscopy combined with cytology is used as diagnostic gold standard for bladder cancer surveillance and those suspicious for the disease. Although cystoscopy with cytology is favored by its high sensitivity for most tumors, it is practically limited at some instances. Its application is limited by its inability to sometimes recognize smaller lesions, and carcinoma in situ. Procedures are also invasive causing anxiety in patients and cystoscopic monitoring is not cost effective.,
The search for noninvasive indicators of bladder cancer for early detection of incipient lesions is necessitated by its frequent late detection and significant disease-associated morbidity and mortality. Over 20 known urine-based biomarkers with high sensitivity and/or specificity have been identified but only bladder tumor antigen (BTA) stat ®, BTA TRAK ®, NMP22, UroVysion ™, and ImmunoCyt ™/uCyt+™ have been approved by the Food and Drug Administration (FDA) for diagnosis and follow-up of bladder cancer.
The BTA test is a test based on specific antibodies recognition of the complement factor H-related protein in voided urine. This protein shares similar structure and function with human complement factor H and is released by self and cultured tumor cells, thus may play an important role in tumor cells’ ability to evade the host’s immune defense system. The BTA test can complement cystoscopy and cytology in bladder cancer diagnosis and therefore can be used to monitor early bladder pathology which could result in urothelial carcinoma.
Diffuse bladder wall thickening (BWT) is commonly diagnosed in patients with abnormal urinary complaints. It is a sign of urinary bladder irritation due to cystitis in the absence of bladder outlet obstruction and signs of neurogenic bladder (radiopedia). The trabeculation of bladder inner wall observable by cystoscopy is considered a sign of detrusor muscle hypertrophy. The use of transabdominal ultrasonography for assessment of BWT is a noninvasive and simple method and has been widely adopted in the last few years., This study will find out the incidence of thickened bladder wall and its association with symptoms of lower urinary tract. Correlation of BTA with BWT which may be an early pathology of bladder cancer is new and has not been reported. The aim of this study therefore was to find out the incidence of thickened bladder wall and its association with BTA and symptoms of lower urinary tract in a low schistosomiasis endemic rural community of Nigeria.

Materials and Methods

The study was conducted in Jewo village within Ijebu North-East Local Government Area in Ogun State, Nigeria. The village has about 300 dwellers. The study area is a typical rural setting lacking in basic amenities such as good roads, electricity, and good water supply. All health-related issues of the dwellers are referred to an underequipped local area community health center located in Ilumafon, a neighboring village which is about 2 km from the study area. The people subsist on river water, which is often polluted by human feces, as a result of lack of toilet facilities.
A descriptive and cross-sectional study was conducted. Due to the limitation of resources, about one-fifth (n = 56) of the total population were selected for participation in the study by simple random sampling. Individuals with history of surgical treatment or instrumentation in about 2 weeks before study were excluded from the study. Previous administration of praziquantel in the last 5 years was also excluded. Only those who gave consent were included.
A questionnaire was administered to determine the demography of the participants, length of stay in the village, and other information related to signs and symptoms of lower urinary tract disease. All questions were asked in Yoruba, the local language of the participants.
Freshly passed mid-day and mid-stream urine samples (collected between 10 and 14 h) of 56 individuals were collected. Ten milliliters of urine sample were collected from each individual, into a well-labeled sterile universal bottle. These were inspected macroscopically for macrohematuria, turbidity, and then screened for microhematuria, bilirubin, urobilinogen, protein, and nitrite using commercially available urine reagent strips (Medi-Test Combi 9®, Neumann-Neander-Str. 6-8. D-52355, ‘Düren). The strip testing was performed in accordance with the manufacturer’s instructions. The urine samples were further processed for parasitological examination and egg count using a standard WHO procedure. Each sample was well mixed and 10 mL of the urine was subjected to centrifugation at 5000 rpm for 5 min. The supernatant was decanted and the sediment was viewed under a light microscope to determine the presence of terminally spined S. haematobium eggs.
Subsequently, pelvic ultrasound examination was carried out on each individual by a consultant radiologist, after ensuring a full (well distended) urinary bladder. The examinations was done blind to the individuals’ S. haematobium infection statuses. The volunteers were examined using a Mindray, DP2200 portable ultrasound apparatus with a 3.5 MHz curvilinear probe. Diffuse bladder wall thickness greater than 3 mm was diagnosed as thickened.
Urine samples (10 mL) collected separately for BTA analysis was centrifuged, and about 2 mL of the supernatant was stored at −20°C. Human BTA enzyme-linked immunosorbent assay (ELISA) Kit (Catalog No: E-EL-H0579, Elabscience, China) which uses the Sandwich-ELISA principle was used. This test was performed in accordance with the manufacturer’s instructions and blinded to S. haematobium and bladder wall thickness results. Briefly, 100 μL standard of the sample was added to each well and incubated for 90 min at 37°C. Supernatant was removed and 100 μL of biotinylated detection antibody was added and then incubated for 1 h at 37°C. The well content was aspirated and washed 3 times. 100 μL of avidin-horseradish peroxidase conjugate was added and incubated for 30 min at 37°C. The well content was aspirated and washed 5 times. Substrate reagent (90 μL) was added followed by incubation at 37°C for 15 min. Stop solution (50 μL) was added, and the plate was read immediately at 450 nm wavelength. The BTA values were graded as 0.476–1.182, 1.183–5.320, and 5.321–14.867 ng/mL for low, moderate, and high level, respectively.
Permission was sought from the communities’ leaders before study. Communities’ heads were contacted in advance of the survey to ensure maximum participation of the participants. Oral informed consent was obtained from adult participants, and in case of children, consent was obtained through their parents or guardians. The study was voluntary, and participants were permitted to opt out at any time. Ethical approval was obtained from Babcock University Research Ethics Committee.
Data generated was analyzed using GraphPad Prism 5 (GraphPad Software, Inc., La Jolla, CA, USA). Chi-square analysis and Fisher’s exact test were used to test for association between occurrence of bladder pathology, BTA, and lower urinary tract symptoms (LUTS). Sensitivity of bladder pathology and symptoms of urological disorder in diagnosing BTA was calculated. The sensitivity of symptoms of urological disorder in diagnosing bladder wall thickness was also determined. P < 0.05 was considered statistically significant.

Results

The prevalence of urogenital schistosomiasis in the area was 3.6%. The overall prevalence of positive human BTA in the individuals was 44.6% with 14.3%, 16.1%, and 14.3%, representing the proportion of low, moderate, and high urinary BTA in the individuals, respectively. BWT (35.7%) was the most prevalent bladder pathology while bladder wall contracture (1.8%) was the least. The overall prevalence of LUTS was 64.3%. Urgency, dysuria (16.1% each), and frequency (3.6%) were the most and least reported LUTS, respectively. There was an association between LUTS and BWT (P = 0.004; odds ratio = 6.0; 95% confidence interval = 1.8–20.3). BTA, BWT, and LUTS were not gender and age dependent (P > 0.05) although higher values were recorded in male participants in BTA (54.5%), BWT (39.4%), and some other LUTS than in their female counterparts. In addition, there was no association between urinary BTA, occurrence of BWT, and LUTS (P > 0.05). Individuals who had stayed between 6 and 10 years in the study area showed highest BTA occurrence in urine (50.0%). BTA occurrence was not associated with duration of stay in the community. BWT was also highest (45.0%) in individuals who had stayed between 6 and 10 years in the villageand was generally not associated with duration of stay (P > 0.05).

Table 1: Occurrence of bladder tumor antigen and indicators of urological disorder with respect to sex and age
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Table 2: Associations between bladder tumor antigen and indicators of urological disorder
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Table 3: Association between bladder tumor antigen and duration of stay in the community

Table 4: Association between bladder wall thickness and duration of stay in the community

In single assessment of clinical examination of bladder and symptoms of urological disorder, dysuria (55.6%), urgency (55.6%), and suprapubic pain (57.1%) were the most sensitive in indirect diagnosis of urinary BTA . Sensitivity was improved (60.0%) when clinical examination (BWT) was combined with other self-reported LUTS . The frequency of urination (0.0%) was not sensitive in diagnosing BWT. Nocturia (75.0%) was the most sensitive self-reported LUTS for indirect diagnosis of BWT .

Table 5: Sensitivity of bladder pathology and symptoms of urological disorder in diagnosing bladder tumor antigen

Table 6: Sensitivity of symptoms of urological disorder in diagnosing bladder wall thickness

Discussion

This study is the first to correlate positive human urinary BTA with bladder structural pathology and LUTS with a view to monitoring the pathophysiology of bladder pathology at the community level. The study area showed low endemicity of S. haematobium unlike Ilumafon, a nearby village which showed a 20% prevalence level in an unpublished preliminary study. The few cases of schistosomiasis in our study area were due to imported infection from endemic areas. Although BTA has not been directly linked with Schistosoma- induced bladder cancer, other urinary biomarkers such as BLCA-4 test (urine) and nuclear morphometry or quantitative nuclear grading of epithelial cells (urine sediment) have been explored. These biomarkers were used to evaluate specific effects of long-term exposure to S. haematobium., The low schistosomiasis cases in the present study made it difficult to correlate the disease with urinary BTA and BWT.
The similar patterns in BTA and BWT occurrence in male and female individuals could suggest some correlations in the etiologies of the two abnormalities. Their higher occurrences, especially in the male individuals, are indications of higher risk of exposure or practices that could potentiate these conditions. Smoking and alcoholism are two important practices noticed among some of the adult male individuals in the area. These practices could work synergistically to suppress the immune system and increase exposure to urinary tract infections (UTIs), thus resulting in the observed higher bladder pathology and LUTS in the male individuals. Higher positive BTA and BWT in children compared with the adults could be associated with higher exposure to the risk factors. Higher rate of UTIs in the group could be the likely cause of higher occurrence of BWT which could in turn increase the urinary BTA level. The zero prevalence of nitrite in urinalysis results could indicate product’s inability to detect it and the need to carry out standard microbiological tests to detect UTIs in the individuals. The prevalence of LUTS reported in our study is higher than in a previous study conducted on some Southwestern men but lies within the range (13%–67%) documented in previous epidemiologic surveys across the world., Dysuria and urgency which are the most frequently reported symptoms have been previously documented as some of the most frequent LUTS in Nigerian population.
The lack of associations between BTA or BWT occurrence and duration of stay in the community suggests that the risk factors for these disorders are not localized to the community. Smoking, alcoholism, and exposure to UTIs have been earlier suggested are factors not affected by length of stay in the present or previous individuals’ locations. Although urinary BTA occurrence was not generally dependent on the LUTS, pain-associated symptoms such as dysuria and suprapubic pain seem to increase the risk of urinary BTA. This is further supported by the moderate sensitivity of the two symptoms for indirect diagnosis of BTA. However, this observation needs further investigation with a larger sample size. Poor sensitivity of BWT to indirectly diagnose BTA is not desirable as individuals with significant BTA levels could be left unnoticed and this could eventually prone them to the risk of urothelial carcinoma. False-positive BTA results associated with some genitourinary conditions such as hematuria as reported by the individuals or diagnosed during urinalysis could be the cause of this low sensitivity. The false-positive result could be caused by the reaction of complement factor H in the urinary blood with the antibody in the test kit., In practice, the combination of BWT and LUTS to indirectly diagnose abnormal BTA level can be useful owning to the observed improved sensitivity. While nocturia was sensitive for diagnosing BWT, the combination of all the symptoms gave better specificity.

Conclusion

This study showed that schistosomiasis is not endemic in our study area and the few encountered cases of S. haematobium infection were imported from endemic areas during the previous visit or stay in the areas. The relationship between BTA, BWT, and schistosomiasis therefore cannot be studied owning to this limitation. The high occurrence of BTA and BWT in the individuals indicates high risk of urothelial carcinoma and urinary bladder irritation, respectively. Combination of BWT and other self-reported LUTS could moderately diagnose BTA in urine. The role of urogenital schistosomiasis in urinary BTA levels needs to be further explored.
Acknowledgments
We acknowledge the co-operation of the villagers. Also, Dr. Chibundu Ezekiel for proofreading the manuscript.
Financial support and sponsorship
This study was funded by a Babcock University Research Grant (BU/RIIC/2016/005) awarded to OO.
Conflicts of interest
There are no conflicts of interest.

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Tables

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Jenifer Donnelly.jpeg

Jenifer Donnelly had none of the classic risk factors for bladder cancer and she warns others not to ignore symptoms that don’t fit with the disease.

(Courtesy of the Donnelly family)

Tom Harbert, who died Dec. 1, battled invasive bladder cancer that he believed resulted from a medication he took for diabetes.

For more than a year, Jenifer Donnelly put up with the uncomfortable symptoms of a urinary tract infection that many women know all too well – urgency, frequency, burning. But when doctors looked further she received an unexpected diagnosis: Bladder cancer.

“No one in my family had bladder cancer. One of the first signs of it is blood in the urine and I never had that,” said the 55-year-old Lower Paxton Township woman who was diagnosed in March 2011.

When she sought help at a gastroenterologist who ordered a CT scan, it showed a thickened bladder wall. A cystoscopy procedure to look inside the bladder and take a biopsy found a low-grade bladder cancer that, luckily, had not penetrated the muscle wall.

The good news with bladder cancer is that 70 percent of newly-diagnosed bladder cancers are early stage and very treatable, according to Dr. Jongming Li, an oncologist with PinnacleHealth System.

About 75,000 Americans are diagnosed with bladder cancer annually and about 15,600 American die from it each year, according to the American Cancer Society. The majority of people diagnosed are older than age 55 and the average age at time of diagnosis is 73.

Former state legislator Mike Waugh, who was most recently the executive director of the Pennsylvania Farm Show Complex and Expo Center in Harrisburg, died in October after a long battle with bladder cancer.

The No. 1 risk factor for bladder cancer is smoking.

“Carcinogens from smoking get into the urine and can damage the lining of the bladder,” Li said “This is critical information to know. If you smoke, you are three times as likely to get bladder cancer.”

Men are three to four times more likely to develop bladder cancer and it’s the fourth leading cancer in men, but Dr. R. Scott Owens, urologist with Urology of Central PA, said his practice has been seeing increased numbers of younger people being diagnosed and more women, perhaps because more women are smoking.

Abnormal symptoms possible

Donnelly defies many things common among bladder cancer victims – she was younger than 55 when diagnosed; she’s a woman and she never smoked. Her parents, however, both smoked, which makes her wonder about the impact of second hand smoke. A graphic designer, she also has none of the chemical exposures linked to bladder cancer.

She was given an immunotherapy treatment called Bacillus Calmette-Guerin, or BCG therapy, an effective immunotherapy for treating early-stage bladder cancer.

The body’s immune system sees the BCG, a bacterium related to tuberculosis that is put directly into the bladder through a catheter, and attacks it and also kills the cancer cells, Owens said.

After several rounds of BCG, “I think my bladder just threw up its hands and said ‘I’m done,'” said Donnelly, who suffered with ongoing cystitis that had similar symptoms to her original ones even when her cancer was at bay from January 2012 to September 2014. She took steroids and antibiotics to manage it.

Then this fall, tests showed recurrence of a low-grade malignancy. She now takes a chemotherapy drug called docetaxel that is not supposed to irritate her bladder like some of the other chemotherapy drugs used for bladder cancer.

“I’m back to square one again, but it’s still non-invasive. It just wears on you a bit because it’s always there,” she said.

Invasive type less common

Unlike Donnelly, Tom Harbert unfortunately has the worst kind of bladder cancer – invasive into the bladder wall. The 51-year-old Hampden Township man passed away Dec. 1, surrounded by his family.

As in Donnelly’s case, Harbert’s symptoms were not classic for bladder cancer. He had abdominal cramps and gas pains that eventually became so severe that he was sent for a CT scan that revealed a tumor in his bladder that was already through the bladder wall.

His only option was to have his bladder removed. Rather than have chemotherapy before surgery, the bladder was removed first due to the aggressiveness of his cancer, he said. He woke up not with the internal neobladder made from intestine that he expected but with a urostomy pouch.

“When the doctor saw how invasive the cancer was, they didn’t want to wait for a neobladder to heal. They wanted me to start on chemo as quickly as I could,” Harbert said in November. The cancer had spread to his peritoneal area and his lymph nodes were visibly cancerous as well.

On strong pain medications and nearing death, Harbert wanted to be interviewed to warn other people not to ignore symptoms abnormal for bladder cancer.

Although he didn’t smoke and wasn’t around chemicals, Harbert was diabetic and had taken a drug called Actos for 10 years. It has been linked to bladder cancer, with a recent study suggesting that it more than doubles the risk of bladder cancer for people who take it more than a year.

“When you have a symptom, don’t sit on it,” Harbert said, adding it “hurt him a lot” to think that a drug that was supposed to help him may have claimed his life.

Harbert was told from the beginning that he had a very small chance of survival. He took chemotherapy and was cancer-free for nine months at one point. He was still plagued by constant urinary tract infections. Harbert said the loss of strength, hearing and cognitive abilities caused by the chemotherapy almost made him wish he had not taken it.

“It’s our goal as a family to do what we can because we don’t want anyone else to go through this,” said his wife of 22 years, Cindy Harbert. “There’s something about a bladder that people don’t like talking about it, but everyone’s got one and everyone goes to the bathroom. People have to understand bladder cancer exists and know the risk factors.”

The couple said they relied heavily on their faith to deal with Tom’s diagnosis.

“But we have two daughters who are 20 and 15 and they’re going to have a life without their dad,” Cindy Harbert said. “That’s been the most difficult thing to swallow.”

Study questions biopsy quality

A recent UCLA study published in the journal “Cancer” showed for the first time that when patients fail to get optimal biopsies, the disease is wrongly staged, meaning it is not recognized as being in an advanced a state. This leads to the treatment being less aggressive than warranted, increasing the chance the patient will die, the study found.

The two-year study looked at some 2,000 patients diagnosed with “non-invasive” bladder cancer and found that about half of them had biopsies that did not contain enough bladder wall muscle to accurately stage the cancer.

Doctors are cautious when taking biopsies because the bladder wall is thin and can be easily perforated, Li said.

“Oftentimes, we do see the urologist did not get enough tissue, but you can’t blame them. They don’t want to perforate,” he said. “They often go back for more tissue, but there is a limit on human abilities to do these things.”

Researchers said they hope their findings will empower patients to question their doctors about the quality of their biopsies and request repeat biopsies.

Owens said he thinks the study is actually more important for doctors than patients. He added that he doesn’t think wrongly-staged cancer is the reason why there isn’t a better survival rate for bladder cancer.

“I think a good wake-up call to urologists to make sure we get muscle if there are signs that the cancer is invasive,” he said. “However, to take every patient and every tumor and say you have to have muscle taken is overaggressive because most are superficial. It’s a patient-by-patient analysis.”

Patient Education

When Your Child Has Neurogenic Bladder

Your child has been diagnosed with neurogenic bladder. This is a problem with the nerves that carry signals to and from your child’s bladder. It can lead to trouble with holding or releasing urine. Neurogenic bladder can be managed. Your child’s healthcare provider will tell you more about options for your child.

What is neurogenic bladder?

Normally, nerves carry messages back and forth between the bladder and the brain. The nerves tell the brain when the bladder is full. The brain then sends signals, telling the bladder muscles to hold or release urine. With neurogenic bladder, the messages aren’t being sent or received properly. This can lead to problems with bladder control.

What causes neurogenic bladder?

Damage to nerves may be caused by the following:

  • Nerve problems that are present at birth (congenital), such as spina bifida

  • Injury to or infection of the brain or spinal cord

What are the signs?

These are the signs of neurogenic bladder:

  • Trouble holding or releasing urine

  • Failure to potty train

  • Urinary tract infection (UTI)

  • Swollen kidneys or other congenital urinary problems

  • Thickened bladder wall

How is neurogenic bladder diagnosed?

Neurogenic bladder is often suspected in children with conditions or injuries affecting the brain or spinal cord. Your healthcare provider will ask you about your child’s health. A physical exam will also be done to look for problems and observe urination. To help get more information:

  • Urine tests may be done to detect an infection and protein in the urine. Protein in urine can be a sign of kidney disease.

  • You may be asked to keep a record of your child’s voiding habits.

  • A kidney and bladder ultrasound may be used to check for swelling of the kidneys and look at the bladder.

  • A urodynamics study may be done to give the healthcare provider a detailed look at how well your child’s bladder and urethra work.

How is neurogenic bladder treated?

Treatment depends on the cause of your child’s neurogenic bladder and what type of voiding problem he or she has. Your child may need one or more of the following treatments:

  • Timed voiding, which means using the toilet at regularly scheduled times. It can help your child avoid wetting accidents and protect the kidneys.

  • Intermittent catheterization to drain the bladder on a regular schedule. It involves inserting and removing a tube (catheter) through the urethra into the bladder each time it needs to be emptied.

  • For some injuries, a more permanent catheter placement called an indwelling catheter is needed.

  • Medicine to relax the bladder muscles and prevent muscle spasm (involuntary tightening of muscles).

  • Surgery to protect the kidneys and allow for continence (the controlled holding in and releasing of urine and stool). Surgery may be done to:

    • Create a new opening in the belly through which a temporary catheter can be placed to empty the bladder

    • Make the bladder larger

    • Tighten the sphincter so it can better hold in urine

Your child’s healthcare provider can discuss surgery with you, if it is an option.

Timed voiding

Timed voiding means urinating at scheduled times. It allows kids who are potty trained to empty their bladders on a regular basis. This helps prevent infections and avoid wetting accidents. To practice timed voiding, your child will need to visit the bathroom at set times throughout the day. His or her healthcare provider can suggest how often your child should urinate. Your child should NOT wait until the urge to urinate arises before using the toilet.

What are the long-term concerns?

Left untreated, children with this condition are likely to have bladder and kidney problems. Constipation and the inability to hold in stool may also be more likely. Steps can be taken to help with these problems. Your child’s healthcare provider can discuss your child’s condition with you and how your child is likely to progress long-term. Also, the condition may change over time so it will need to be monitored throughout your child’s lifetime.

Coping

Dealing with neurogenic bladder can be difficult to cope with. Incontinence can also cause embarrassment and lead to self-esteem issues for your child. It’s vital for your child’s treatment and emotional development that you be supportive and patient. It takes work and time to learn how to best manage your child’s condition. Encourage your child’s success by seeing to it that he or she follows the treatment plan. In some cases, a psychological therapist can help the child and family follow the treatment plan.

Learning more

If you have questions, talk to your child’s care team. Also, look for support materials in your local library or bookstore. These online resources can also be helpful:

  • National Association for Continence www.nafc.org

  • Spina Bifida Association www.spinabifidaassociation.org

Bladder Cancer

Blue Light Technology in Bladder Cancer Therapy

What is bladder cancer?

The bladder, a hollow organ in the lower part of the abdomen, serves as a reservoir for urine until it is discharged out of the body through the urethra.

There are different types of bladder cancer. The cancer cell type can be transitional cell carcinoma, squamous cell carcinoma or adenocarcinoma—each named for the types of cells that line the wall of the bladder where the cancer originates.

  • Most bladder cancers (more than 90 percent) start from the transitional cells, which occupy the innermost lining of the bladder wall. The cancers, which originate in these cells lining the bladder can, in some instances, invade into the deeper layers of the bladder (called the lamina propria), the thick muscle layer of the bladder, or through the bladder wall into the fatty tissues that surround the bladder.
  • Squamous cells are thin flat cells that line the urethra and can form in the bladder after long bouts of bladder inflammation or irritation. Squamous cell carcinoma makes up about 5 percent of bladder cancers.
  • Adenocarcinoma is a very rare type of bladder cancer that begins in glandular (secretory) cells in the lining of the bladder. Only 1 percent to 2 percent of bladder cancers are adenocarcinoma.

What are the stages of bladder cancer?

Bladder cancer can be either early stage (confined to the lining of the bladder) or invasive (penetrating the bladder wall and possibly spreading to nearby organs or lymph nodes).

The stages range from TA (confined to the internal lining of the bladder) to IV (most invasive). In the earliest stages (TA, T1 or CIS), the cancer is confined to the lining of the bladder or in the connective tissue just below the lining, but has not invaded into the main muscle wall of the bladder.

Stages II to IV denote invasive cancer:

  • In Stage II, cancer has spread to the muscle wall of the bladder.
  • In Stage III, the cancer has spread to the fatty tissue outside the bladder muscle.
  • In Stage IV, the cancer has metastasized from the bladder to the lymph nodes or to other organs or bones.

A more sophisticated and preferred staging system is known as TNM, which stands for tumor, node involvement and metastases. In this system:

  • Invasive bladder tumors can range from T2 (spread to the main muscle wall below the lining) all the way to T4 (tumor spreads beyond the bladder to nearby organs or the pelvic side wall).
  • Lymph node involvement ranges from N0 (no cancer in lymph nodes) to N3 (cancer in many lymph nodes, or in one or more bulky lymph nodes larger than 5 cm).
  • M0 means that there is no metastasis outside of the pelvis. M1 means that it has metastasized outside of the pelvis.

What are the warning signs of bladder cancer?

Some symptoms of bladder cancer are also symptoms of other conditions, and should prompt a visit to your physician. Blood in the urine is the most important warning sign. Pain during urination, frequent urination or difficulty urinating are other symptoms.

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Primer: Diagnosis and Management of Uncomplicated Daytime Wetting in Children

Evaluation of Children With Urinary Incontinence

Evaluation of the child with urinary incontinence typically begins in the office setting (Figure 2). A thorough medical history will delineate the pattern of incontinence and can identify underlying neurologic or anatomic anomalies. The medical history should include information about the child’s voiding habits, including straining, urinary frequency, urination posture, pain with urination, and associated constipation or infection. An obstetric history should be taken to reveal evidence of fetal distress, anoxia, birth trauma, prenatal hydronephrosis, or oligohydramnios. A history of developmental delay, impaired upper or lower motor skills, and associated encopresis raises the suspicion of a neurologic etiology for urinary incontinence. Finally, a family history and social history might be useful in the assessment of underlying medical conditions or stressors that might contribute to urinary incontinence.

If the patient’s initial medical history, physical examination, or urine studies suggest an abnormality, a renal and/or bladder ultrasound, and urine flow rate with pelvic floor electromyogram should be obtained. Voiding cystourethrography is reserved for cases in which an anatomic or neuropathic etiology is considered, or when vesicoureteral reflux is suspected. Cystometrography rarely has a role in the evaluation of functional daytime incontinence. This investigation is reserved for severe cases of dysfunctional voiding, and when a neuropathic etiology is considered. Abbreviations: EMG, electromyography; VCUG, voiding cystourethrography.

A 3-day voiding and defecation diary is a useful tool to define the severity and frequency of incontinence episodes, as well as the presence or absence of constipation. The voiding diary should include an assessment of fluid intake.

Physical examination should include an inspection of the abdomen, genitalia and spine, as well as a directed neurologic examination, which should include an assessment of lower extremity muscle tone and strength, gait, and symmetry of lower extremity reflexes. The abdomen should be palpated to determine the presence of suprapubic fullness suggestive of bladder distension. A palpable left lower quadrant mass can indicate fecal impaction. A genital examination might disclose the presence of labial adhesions, vulvovaginitis, ectopic ureter, or abnormal urethral position in girls and abnormalities of the urethral meatus in boys. The lower back is inspected for scoliosis as well as stigmata of occult spinal dysraphism, such as sacral dimple, hair tuft, hemangioma, or lipoma. The coccyx should also be examined for evidence of sacral agenesis. The lower extremities and gluteal folds should be evaluated for asymmetry, which might be evidence of tethered cord syndrome.

Urinalysis is an important part of the initial evaluation of children with lower urinary tract dysfunction. Evidence of urinary tract infection, such as bacteriuria or pyuria, might require additional radiographic evaluation. Specific gravity of a first morning urine sample is useful in the evaluation of urine-concentrating ability, while urine glucose levels can identify diabetes mellitus. Presence of hematuria might also elicit additional radiographic or laboratory evaluation.

The need for additional imaging and functional studies is determined by findings from the patient’s history and physical examination. Abdominal radiography is useful as an objective measure of constipation. In children with demonstrable neurologic or lumbosacral abnormalities on physical examination, an MRI is required in order to evaluate structural anomalies of the spinal cord.

Renal ultrasound is an excellent screening tool for patients with functional daytime incontinence. Ultrasonography is useful in the detection of structural abnormalities of the kidneys and bladder, such as hydronephrosis, ureterectasis, ureterocele, and bladder wall thickening (Figure 3). Children with recurrent or febrile urinary tract infections or bladder wall thickening, observed on ultrasound, should undergo voiding cystourethrography (VCUG). This procedure allows evaluation for vesicoureteral reflux, and structural abnormalities of the urethra in boys.

Ultrasound showing bladder-wall thickening in a 6-year-old female with recurrent urinary infections, vesicoureteral reflux, and daytime wetting. Normal bladder wall thickness should be less than 2 mm in normal children with a distended bladder; this child has a bladder-wall thickness of 5.2 mm.

VCUG should be used in children with suspected dysfunctional voiding. Children who fail to relax the urethral sphincter during voiding often have a ‘spinning top’ urethral configuration. This appearance is due to a failure to relax the external sphincter during voiding, causing dilation of the proximal urethra. In children with infrequent voiding, VCUG could reveal a large capacity, smooth-walled bladder with a significant PVR volume. Males with dysfunctional voiding should undergo a careful evaluation of the urethra during the voiding phase, to rule out obstructive abnormalities of the urethra.

A number of physiologic tests are available that evaluate bladder and sphincter function. The urine flow rate is an indirect measure of bladder and sphincter function, which is often used in conjunction with pelvic-floor electromyography, to evaluate pelvic-floor activity during voiding. Invasive urodynamic studies such as cystometrography and videourodynamics rarely add to the management of patients with milder forms of functional incontinence, and should be reserved for those patients with complex forms of functional urinary incontinence such as non-neurogenic neurogenic bladder syndrome.

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